Elucidation of molecular mechanism on thyroid carcinogenesis anddevelopmental application of molecular targeting therapy

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We have successfully established a cell culture system from primary human thyroid tissues and identified the multi-potential stem cell-like cells in a specific serum-free medium condition. One speculates that there is a profound relationship of reprogramming and mesenchymal transition between stem cell-like cells and differentiated cells from thyroid tissues. These findings may suggest a new aspect and relationship of thyroid cancer stem cells during its carcinogenesis. Furthermore we have studied the functional role of FOXE1 that is a major thyroid cancer-associated SNP gene. Using immunohistochemistry, specific patterns of FOXE1 expression in thyroid carcinomas have been identified. We have separately clarified a strong association between the SNPs of FOXE1 and NKX-2, and the Japanese thyroid cancer cases. This is the first report on the different ethnics besides Caucasians. Finally we found the new evidence of imanitib, a molecular targeting agent, selectively inhibited an increase of NFkappa B activity induced by irradiation in cultured thyroid cancer cell lines. The combination chemotherapy with radiation may become more efficient therapeutic approach for a poor-prognosis thyroid anaplastic cancer patient clinically.